Infliximab is a chimeric IgG1κ monoclonal antibody, which is a type of protein that recognizes, attaches to, and blocks the action of tumor necrosis factor-alpha (TNF-alpha). Infliximab is currently sold under the tradename REMICADE by Centocor Ortho Biotech, Inc., in Horsham, Pa. Infliximab has been used for the treatment of inflammatory disorders, such as plaque psoriasis, rheumatoid arthritis, psoriatic arthritis, adult Crohn's disease, pediatric Crohn's disease, ulcerative colitis, and ankylosing spondylitis. Currently, infliximab is given by IV infusion and it's half-life is approximately eight weeks. Initially, patients receive three infusions (5 mg/kg) given at 0, 2 and 6 weeks. Following, the patients are dosed (5 mg/kg) every eight weeks. Due to frequent dosing and patient visits to the clinic, the cost associated with infliximab is high.
Therefore, there is a need for a controlled release device for infliximab to eliminate the frequent dosing and doctor visits for the patient and provide a cost effective treatment. Standard methods for preparing controlled release devices include the use of polymeric matrices, typically in the form of microspheres, rods, sheets or pellets, which are used to encapsulate the active agent. A variety of techniques are known by which active agents can be incorporated into polymer matrices. Examples include solvent evaporation, spray drying, emulsification, melt blending and simple physical mixing of particles of discrete size or shape. None of these approaches may be applied to incorporate peptides or proteins into the polymers due to the delicate nature of these molecules. Peptides and proteins are susceptible to denaturation by solvents, by emulsification, by heat and, in particular, by terminal sterilization.
Therefore, there is a need for a method of making a controlled release device for infliximab, where the method does not denature or otherwise inactivate the activity of the protein. A controlled release device for infliximab is also desired which provides a localized, sustained release of the protein, eliminates the need for frequent dosing and doctor's visits for the patient, and provides a cost effective treatment.